Memantine

Identification

Summary

Memantine is an NMDA receptor antagonist used to treat moderate to severe dementia in Alzheimer's.

Brand Names
Axura, Ebixa, Marixino, Namenda, Namenda 49 Titration Pack, Namzaric
Generic Name
Memantine
DrugBank Accession Number
DB01043
Background

Initially approved by the FDA in 2013, memantine is an N-methyl-D-aspartate (NMDA) receptor antagonist used in the management of Alzheimer's Disease (AD). It is different from many other Alzheimer's Disease medications, as it works by a different mechanism than the cholinesterase enzyme inhibitors normally employed in the management of Alzheimer's disease 2. Memantine blocks the effects of glutamate, a neurotransmitter in the brain that leads to neuronal excitability and excessive stimulation in Alzheimer's Disease 9.

In 2010, it was estimated that 36 million people worldwide live with Alzheimer's Disease. In 2013, this number increased to 44 million. Almost doubling every 20 years, the prevalence of Alzheimer's Disease is predicted to reach 66 million by 2030 and to 115 million by 2050 13. In December 2013, the G8 dementia summit concluded that dementia should be considered a global priority with the objective of developing a cure or a disease-modifying therapy by the year 2025 10,13.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 179.3018
Monoisotopic: 179.167399677
Chemical Formula
C12H21N
Synonyms
  • 1-Amino-3,5-dimethyladamantane
  • 1,3-Dimethyl-5-adamantanamine
  • 3,5-Dimethyl-1-adamantanamine
  • 3,5-Dimethyl-1-aminoadamantane
  • 3,5-Dimethyltricyclo(3.3.1.1(3,7))decan-1-amine
  • Memantina
  • Memantine
  • Memantinum
External IDs
  • D-145
  • DRG-0267

Pharmacology

Indication

Memantine is used to manage moderate to severe Alzheimer's dementia Label.

A more recent systemic review and meta-analysis 6 indicates that memantine is beneficial as a first line drug for the treatment of Alzheimer's dementia. Cholinesterase inhibitors may be added to memantine for further beneficial effects on behavioral symptoms and other symptoms of dementia 6.

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Used in combination to treatAlzheimer's disease (ad)Combination Product in combination with: Idebenone (DB09081)••••••••••••••••••• ••••••
Used in combination to treatModerate-to-severe alzheimer's diseaseCombination Product in combination with: Ginkgo biloba (DB01381)••••••••••••••••••• ••••••••••••
Management ofMild vascular dementia••• •••••
Used in combination to manageModerate alzheimer's type dementiaCombination Product in combination with: Donepezil (DB00843)••••••••••••
Management ofModerate vascular dementia••• •••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

General effects

This drug inhibits calcium influx into cells that is normally caused by chronic NMDA receptor activation by glutamate 3. This leads to the improvement of Alzheimer's dementia symptoms, demonstrated by increased cognition and other beneficial central nervous system effects 3.

Effects on neuroplasticity

Like other NMDA receptor antagonists, memantine at high doses can reduce neuronal synaptic plasticity that is involved in learning and memory processes. At lower concentrations, which are normally used in the clinical setting, memantine can enhance neuronal synaptic plasticity in the brain, improve memory, and act as a neuroprotectant against the destruction of neurons caused by excitatory neurotransmitters 2.

Effect on various receptors

Memantine has demonstrated minimal activity for GABA, benzodiazepine, dopamine, adrenergic, histamine, and glycine receptors, as well as voltage-dependent Ca2+, Na+ or K+ channels. This drug has shown antagonist activity at the 5HT3 receptors. Laboratory studies suggest that memantine does not affect the reversible inhibition of the acetylcholinesterase normally caused by donepezil, galantamine, or tacrine Label.

Mechanism of action

Continuous activation of the N-methyl-D-aspartate (NMDA) receptors in the central nervous system caused by glutamate is thought to cause some of the Alzheimer's disease symptoms. This overactivation is thought to contribute to neurotoxicity due to the excitatory properties of glutamate 9. The pharmacological effect of memantine likely occurs via the drug's behavior as an uncompetitive (open-channel) NMDA receptor antagonist, preventing glutamate action on this receptor. Memantine has a preference for the NMDA receptor-operated cation channels. Despite these antagonist effects, memantine has not been proven to prevent or retard the neurodegeneration seen in patients diagnosed with Alzheimer’s disease Label.

TargetActionsOrganism
AGlutamate (NMDA) receptor
antagonist
Humans
U5-hydroxytryptamine receptor 3A
antagonist
Humans
UNeuronal acetylcholine receptor subunit alpha-7
antagonist
Humans
UDopamine D2 receptor
antagonist
agonist
Humans
UGlutamate receptor ionotropic, NMDA 1
binder
Humans
UGABA(A) Receptor
binder
Humans
UGlycine receptors
inhibitor
Humans
Absorption

After an oral dose, memantine is well absorbed. Its peak drug concentrations are attained in about 3-7 hours. Memantine shows linear pharmacokinetics when given at normal therapeutic doses. This drug can be taken without regard to food, as there is no effect of food on memantine absorption Label.

Volume of distribution

The mean volume of distribution of memantine is 9-11 L/kg Label.

Protein binding

The protein binding for memantine is about 45% Label.

Metabolism

This drug is partially metabolized in the liver. The hepatic CYP450 enzyme system does not majorly contribute to the metabolism of this drug Label.

Hover over products below to view reaction partners

Route of elimination

This drug is mainly excreted in the urine. Approximately 48% of administered memantine is excreted unchanged in urine Label.

The remainder of the drug is metabolized to three main metabolites. These metabolites are the N-glucuronide conjugate, 6-hydroxy memantine, and 1-nitroso-deaminated memantine, which show minimal NMDA receptor antagonist activity Label.

Half-life

The terminal elimination half-life of memantine ranges from 60 to 80 hours in humans.8,12

Following administration of a single oral dose of 10 mg/kg memantine in rats, the elimination half-life was 2.36 ± 0.20 hours. Following a single intravenous dose of 2 mg/kg in rats, the elimination half-life was 2.28 ± 0.48 hours.7

Clearance

This drug is cleared by active tubular secretion in the kidneys. Tubular reabsorption of this drug is pH dependent Label.

Adverse Effects
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Toxicity

LD50

Oral LD50, mouse 437-498 mg/kg 14 Oral LD50, rat 328-370 mg/kg 14

Carcinogenesis, Mutagenesis, Impairment of Fertility

No evidence of carcinogenicity was seen in mouse and rat models administered memantine at doses equivalent to supratherapeutic human doses Label. Additionally, no genotoxic potential was noted when a battery of assays was performed. No effects on fertility or reproductive performance were noted in rats given to 18 mg/kg/day (equivalent to 9 times the maximum recommended human dose) orally from 14 days preceding mating through gestation and lactation in females, or for 60 preceding mating activity in males animals Label.

Use in pregnancy

This drug is considered a pregnancy category B drug, meaning no sufficiently controlled and adequate studies of memantine in pregnant women have been performed. This drug should be taken during pregnancy only if the potential benefit justifies the possible fetal risk Label.

Use in nursing

It is unknown whether memantine is excreted in human milk. Due to that fact that many drugs are found excreted in human milk, caution should be observed when this drug is taken by a nursing mother Label.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirMemantine may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbrocitinibThe metabolism of Abrocitinib can be decreased when combined with Memantine.
AcebutololMemantine may increase the bradycardic activities of Acebutolol.
AceclofenacAceclofenac may decrease the excretion rate of Memantine which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Memantine which could result in a higher serum level.
Food Interactions
  • Take with a full glass of water.
  • Take with or without food. The absorption is unaffected by food.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Memantine hydrochlorideJY0WD0UA6041100-52-1LDDHMLJTFXJGPI-UHFFFAOYSA-N
Product Images
International/Other Brands
Abixa / Akatinol / Memox
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Act MemantineTablet10 mgOralTEVA Canada Limited2010-02-18Not applicableCanada flag
Act MemantineTablet5 mgOralTEVA Canada LimitedNot applicableNot applicableCanada flag
AxuraTablet, film coated20 mgOralMerz Pharmaceuticals2016-09-08Not applicableEU flag
AxuraTablet, film coated20 mgOralMerz Pharmaceuticals2016-09-08Not applicableEU flag
AxuraTablet, film coated10 mgOralMerz Pharmaceuticals2016-09-08Not applicableEU flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Apo-memantineTablet10 mgOralApotex Corporation2011-06-17Not applicableCanada flag
Jamp-memantineTablet10 mgOralJamp Pharma Corporation2015-02-03Not applicableCanada flag
Jamp-memantineTablet5 mgOralJamp Pharma CorporationNot applicableNot applicableCanada flag
MemantineTablet10 mg/1OralMajor Pharmaceuticals2015-07-20Not applicableUS flag
MemantineTablet5 mg/1OralNorthstar RxLLC2022-09-13Not applicableUS flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
BERMAXIN 90/10/5 MG FILM TABLET ,FILM TABLET, 28 ADETMemantine hydrochloride (5 mg) + Donepezil hydrochloride (10 mg) + Idebenone (90 mg)Tablet, film coatedOralCELTİS İLAÇ SAN. VE TİC. A.Ş.2014-03-31Not applicableTurkey flag
BERMAXIN 90/10/5 MG FILM TABLET ,FILM TABLET, 84 ADETMemantine hydrochloride (5 mg) + Donepezil hydrochloride (10 mg) + Idebenone (90 mg)Tablet, film coatedOralCELTİS İLAÇ SAN. VE TİC. A.Ş.2014-03-31Not applicableTurkey flag
COGİTO 5+10+15+20 MG FİLM KAPLI TABLET TEDAVİYE BAŞLAMA PAKETİ, 28 TABLETMemantine hydrochloride (5 mg) + Memantine hydrochloride (10 mg) + Memantine hydrochloride (15 mg) + Memantine hydrochloride (20 mg)TabletOralSANTA FARMA İLAÇ SAN. A.Ş.2015-10-20Not applicableTurkey flag
COGİTO 5+10+15+20 MG FİLM KAPLI TABLET TEDAVİYE BAŞLAMA PAKETİ, 28 TABLETMemantine hydrochloride (5 mg) + Memantine hydrochloride (10 mg) + Memantine hydrochloride (15 mg) + Memantine hydrochloride (20 mg)TabletOralSANTA FARMA İLAÇ SAN. A.Ş.2015-10-20Not applicableTurkey flag
COGİTO 5+10+15+20 MG FİLM KAPLI TABLET TEDAVİYE BAŞLAMA PAKETİ, 28 TABLETMemantine hydrochloride (5 mg) + Memantine hydrochloride (10 mg) + Memantine hydrochloride (15 mg) + Memantine hydrochloride (20 mg)TabletOralSANTA FARMA İLAÇ SAN. A.Ş.2015-10-20Not applicableTurkey flag
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Generic DrugMemantine hydrochloride (10 mg/1)TabletOralNingbo Shouzheng Medicinal Research Co., Ltd2020-04-062030-04-17US flag
Generic DrugMemantine hydrochloride (5 mg/1)TabletOralNingbo Shouzheng Medicinal Research Co., Ltd2020-04-062030-04-17US flag

Categories

ATC Codes
N06DA52 — Donepezil and memantineN06DX01 — MemantineN06DA53 — Donepezil, memantine and ginkgo folium
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as monoalkylamines. These are organic compounds containing an primary aliphatic amine group.
Kingdom
Organic compounds
Super Class
Organic nitrogen compounds
Class
Organonitrogen compounds
Sub Class
Amines
Direct Parent
Monoalkylamines
Alternative Parents
Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Aliphatic homopolycyclic compound / Hydrocarbon derivative / Organopnictogen compound / Primary aliphatic amine
Molecular Framework
Aliphatic homopolycyclic compounds
External Descriptors
adamantanes, primary aliphatic amine (CHEBI:64312)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
W8O17SJF3T
CAS number
19982-08-2
InChI Key
BUGYDGFZZOZRHP-UHFFFAOYSA-N
InChI
InChI=1S/C12H21N/c1-10-3-9-4-11(2,6-10)8-12(13,5-9)7-10/h9H,3-8,13H2,1-2H3
IUPAC Name
3,5-dimethyladamantan-1-amine
SMILES
CC12CC3CC(C)(C1)CC(N)(C3)C2

References

Synthesis Reference
US3391142
General References
  1. Cacabelos R, Takeda M, Winblad B: The glutamatergic system and neurodegeneration in dementia: preventive strategies in Alzheimer's disease. Int J Geriatr Psychiatry. 1999 Jan;14(1):3-47. [Article]
  2. Rogawski MA, Wenk GL: The neuropharmacological basis for the use of memantine in the treatment of Alzheimer's disease. CNS Drug Rev. 2003 Fall;9(3):275-308. [Article]
  3. Robinson DM, Keating GM: Memantine: a review of its use in Alzheimer's disease. Drugs. 2006;66(11):1515-34. [Article]
  4. Rogawski MA: Low affinity channel blocking (uncompetitive) NMDA receptor antagonists as therapeutic agents--toward an understanding of their favorable tolerability. Amino Acids. 2000;19(1):133-49. [Article]
  5. Rammes G, Rupprecht R, Ferrari U, Zieglgansberger W, Parsons CG: The N-methyl-D-aspartate receptor channel blockers memantine, MRZ 2/579 and other amino-alkyl-cyclohexanes antagonise 5-HT(3) receptor currents in cultured HEK-293 and N1E-115 cell systems in a non-competitive manner. Neurosci Lett. 2001 Jun 22;306(1-2):81-4. [Article]
  6. Kishi T, Matsunaga S, Oya K, Nomura I, Ikuta T, Iwata N: Memantine for Alzheimer's Disease: An Updated Systematic Review and Meta-analysis. J Alzheimers Dis. 2017;60(2):401-425. doi: 10.3233/JAD-170424. [Article]
  7. Lee SH, Kim SH, Noh YH, Choi BM, Noh GJ, Park WD, Kim EJ, Cho IH, Bae CS: Pharmacokinetics of Memantine after a Single and Multiple Dose of Oral and Patch Administration in Rats. Basic Clin Pharmacol Toxicol. 2016 Feb;118(2):122-7. doi: 10.1111/bcpt.12479. Epub 2015 Sep 28. [Article]
  8. Noetzli M, Guidi M, Ebbing K, Eyer S, Wilhelm L, Michon A, Thomazic V, Alnawaqil AM, Maurer S, Zumbach S, Giannakopoulos P, von Gunten A, Csajka C, Eap CB: Population pharmacokinetic study of memantine: effects of clinical and genetic factors. Clin Pharmacokinet. 2013 Mar;52(3):211-23. doi: 10.1007/s40262-013-0032-2. [Article]
  9. Brianne Kuns; Dona Varghese (2019). StatPearls: Memantine. StatPearls Publishing.
  10. 135 million people will live with dementia worldwide by 2050 [Link]
  11. Sandoz Monograph: Memantine hydrochloride oral tablets [Link]
  12. FDA Approved Drug Products: NAMENDA (memantine hydrochloride) tablets, for oral use [Link]
  13. Alzheimer's disease international: Global Impact of Dementia 2013 [File]
  14. Memantine Product [File]
Human Metabolome Database
HMDB0015177
KEGG Drug
D08174
KEGG Compound
C13736
PubChem Compound
4054
PubChem Substance
46506702
ChemSpider
3914
BindingDB
50062599
RxNav
6719
ChEBI
64312
ChEMBL
CHEMBL807
Therapeutic Targets Database
DAP000493
PharmGKB
PA10364
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Memantine
FDA label
Download (604 KB)
MSDS
Download (65.7 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedNot AvailableAlzheimer's Disease (AD)1
4CompletedBasic ScienceAlzheimer's Disease (AD)1
4CompletedSupportive CareHealthy Volunteers (HV) / Schizoaffective Disorders / Schizophrenia1
4CompletedTreatmentAlcohol Dependency / Depression1
4CompletedTreatmentAlzheimer's Disease (AD)11

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Bryant Ranch Prepack
  • Cardinal Health
  • Coupler Enterprises Inc.
  • Forest Laboratories Inc.
  • Forest Pharmaceuticals
  • Lake Erie Medical and Surgical Supply
  • Lundbeck Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • PD-Rx Pharmaceuticals Inc.
  • Physicians Total Care Inc.
  • Prepackage Specialists
  • Prepak Systems Inc.
  • Ranbaxy Laboratories
  • Rebel Distributors Corp.
  • Resource Optimization and Innovation LLC
  • Stat Rx Usa
  • Vangard Labs Inc.
Dosage Forms
FormRouteStrength
TabletOral15.000 mg
Solution / dropsOral10 mg/g
Tablet, film coatedOral10.0 mg
SolutionOral5 MG
SolutionOral1.0000 g
Tablet, orally disintegratingOral
Kit; tabletOral
Tablet, orally disintegratingOral
Kit; tablet, orally disintegratingOral
Tablet, film coated, extended releaseOral
Tablet, effervescent
Tablet, coatedOral
Tablet, effervescentOral
SolutionOral5 mg/actuation
SolutionOral5 mg/50g
SolutionOral5 mg/100g
TabletOral10.00 mg
Solution / dropsOral
Tablet, effervescent
TabletOral10.000 mg
Tablet, film coatedOral10.00 mg
SolutionOral10 MG/ML
Tablet, film coatedOral15 MG
Tablet, film coatedOral5 MG
Tablet, orally disintegratingOral10 MG
Tablet, orally disintegratingOral20 MG
Tablet, film coatedOral
Tablet, film coatedOral
Capsule, extended releaseOral
Capsule, extended releaseOral21 mg/1
Capsule, extended releaseOral7 mg/1
Capsule, extended release; kitOral
KitOral
LiquidOral2 mg/1mL
SolutionOral10 mg/5mL
Tablet, coatedOral10 mg/1
Tablet, coatedOral5 mg/1
Tablet, film coatedOral10 mg/1
Tablet, film coatedOral5 mg/1
TabletOral10 mg
TabletOral20 mg
TabletOral5 mg
Tablet, coatedOral5 mg
SolutionOral5 mg/ pump actuation
Tablet, film coatedOral10.000 mg
SolutionOral10 MG/G
SolutionOral1.000 g
TabletOral
Capsule, coated pelletsOral14 mg
Capsule, coated pelletsOral28 mg
Capsule, delayed release pelletsOral
SolutionOral2 mg/1mL
TabletOral10 mg/1
TabletOral5 mg/1
Capsule, extended releaseOral14 mg/1
Capsule, extended releaseOral28 mg/1
CapsuleOral
TabletOral20.000 mg
Kit; tablet, film coatedOral
TabletOral5.0 mg
TabletOral
Capsule, liquid filledOral5 mg
Capsule, liquid filledOral10 mg
Capsule, liquid filledOral1000000 mg
SolutionOral1000000 mg
SolutionOral10 mg
Tablet, coatedOral10 mg
Tablet, film coatedOral20 mg
Tablet, coatedOral20 mg
SolutionOral5 mg/0.5ml
Tablet, film coatedOral10 mg
Prices
Unit descriptionCostUnit
Namenda 10 mg tablet3.38USD tablet
Namenda 5 mg tablet3.32USD tablet
Namenda 5-10 mg titration pk3.32USD each
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
CA2426492No2006-10-032023-05-08Canada flag
US8173708Yes2012-05-082026-05-22US flag
US8283379Yes2012-10-092026-05-22US flag
US8362085Yes2013-01-292026-05-22US flag
US8039009Yes2011-10-182029-09-24US flag
US8329752Yes2012-12-112026-05-22US flag
US8598233Yes2013-12-032026-05-22US flag
US8168209Yes2012-05-012026-05-22US flag
US8338486No2012-12-252025-11-22US flag
US8058291No2011-11-152029-12-05US flag
US8580858No2013-11-122025-11-22US flag
US8338485No2012-12-252025-11-22US flag
US8293794No2012-10-232025-11-22US flag
US5061703Yes1991-10-292015-10-11US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)153https://www.lookchem.com/Memantine/
boiling point (°C)239.8https://www.lookchem.com/Memantine/
water solubilitysoluble in waterhttps://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021627lbl.pdf
logP3.28https://www.lundbeck.com/upload/ca/en/files/pdf/pm/Ebixa.pdf
pKa10.27https://www.lundbeck.com/upload/ca/en/files/pdf/pm/Ebixa.pdf
Predicted Properties
PropertyValueSource
Water Solubility0.0455 mg/mLALOGPS
logP3.31ALOGPS
logP2.07Chemaxon
logS-3.6ALOGPS
pKa (Strongest Basic)10.7Chemaxon
Physiological Charge1Chemaxon
Hydrogen Acceptor Count1Chemaxon
Hydrogen Donor Count1Chemaxon
Polar Surface Area26.02 Å2Chemaxon
Rotatable Bond Count0Chemaxon
Refractivity54.49 m3·mol-1Chemaxon
Polarizability21.82 Å3Chemaxon
Number of Rings3Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleYesChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9939
Blood Brain Barrier+0.9823
Caco-2 permeable+0.6082
P-glycoprotein substrateNon-substrate0.6403
P-glycoprotein inhibitor INon-inhibitor0.82
P-glycoprotein inhibitor IINon-inhibitor0.7555
Renal organic cation transporterNon-inhibitor0.7774
CYP450 2C9 substrateNon-substrate0.8213
CYP450 2D6 substrateNon-substrate0.6153
CYP450 3A4 substrateNon-substrate0.5319
CYP450 1A2 substrateNon-inhibitor0.9327
CYP450 2C9 inhibitorNon-inhibitor0.9281
CYP450 2D6 inhibitorNon-inhibitor0.872
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6795
Ames testNon AMES toxic0.6945
CarcinogenicityNon-carcinogens0.7426
BiodegradationNot ready biodegradable0.9633
Rat acute toxicity2.3455 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9839
hERG inhibition (predictor II)Non-inhibitor0.6818
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-03fr-0900000000-4db94b4b87705e834d5d
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-03e9-0900000000-65172d14e0f6b9102d73
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-03di-0900000000-ce475f103d528ff4d342
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-03di-0900000000-1c9199c5cf1c902223ae
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-08fr-0900000000-1bac817f714e7eec7488
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a4i-2900000000-eb58e236084a93a3d37b
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a4i-4900000000-5a87d54400c3e9720ad0
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-052f-9500000000-95eb2b63a2392449ec4a
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0006-9100000000-608b372857aacd60eb61
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00kf-9000000000-f283a81168372575c2aa
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-03di-0900000000-bbf1127413d0f995a000
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-03di-0900000000-54224a7d25c2df813c8a
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-0900000000-3f94c72b4c4afa7b31ff
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-03di-0900000000-9f8fac81fc0cca754762
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-0900000000-3f94c72b4c4afa7b31ff
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-03dj-0900000000-39c63cf83012e305cb61
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-0900000000-06c4e53b08791a69a40a
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-140.6689766
predicted
DarkChem Lite v0.1.0
[M-H]-146.82977
predicted
DeepCCS 1.0 (2019)
[M+H]+141.2046766
predicted
DarkChem Lite v0.1.0
[M+H]+149.18777
predicted
DeepCCS 1.0 (2019)
[M+Na]+140.9065766
predicted
DarkChem Lite v0.1.0
[M+Na]+156.82892
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Protein group
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Voltage-gated cation channel activity
Specific Function
NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine. This protein plays a key role in synaptic p...

Components:
References
  1. Robinson DM, Keating GM: Memantine: a review of its use in Alzheimer's disease. Drugs. 2006;66(11):1515-34. [Article]
  2. Cacabelos R, Takeda M, Winblad B: The glutamatergic system and neurodegeneration in dementia: preventive strategies in Alzheimer's disease. Int J Geriatr Psychiatry. 1999 Jan;14(1):3-47. [Article]
  3. Rogawski MA, Wenk GL: The neuropharmacological basis for the use of memantine in the treatment of Alzheimer's disease. CNS Drug Rev. 2003 Fall;9(3):275-308. [Article]
  4. Memantine FDA label [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
General Function
Voltage-gated potassium channel activity
Specific Function
This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor is a ligand-gate...
Gene Name
HTR3A
Uniprot ID
P46098
Uniprot Name
5-hydroxytryptamine receptor 3A
Molecular Weight
55279.835 Da
References
  1. Rammes G, Rupprecht R, Ferrari U, Zieglgansberger W, Parsons CG: The N-methyl-D-aspartate receptor channel blockers memantine, MRZ 2/579 and other amino-alkyl-cyclohexanes antagonise 5-HT(3) receptor currents in cultured HEK-293 and N1E-115 cell systems in a non-competitive manner. Neurosci Lett. 2001 Jun 22;306(1-2):81-4. [Article]
  2. Nisijima K, Shioda K, Yoshino T, Takano K, Kato S: Memantine, an NMDA antagonist, prevents the development of hyperthermia in an animal model for serotonin syndrome. Pharmacopsychiatry. 2004 Mar;37(2):57-62. doi: 10.1055/s-2004-815526. [Article]
  3. Memantine FDA label [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
General Function
Toxic substance binding
Specific Function
After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane. The cha...
Gene Name
CHRNA7
Uniprot ID
P36544
Uniprot Name
Neuronal acetylcholine receptor subunit alpha-7
Molecular Weight
56448.925 Da
References
  1. Aracava Y, Pereira EF, Maelicke A, Albuquerque EX: Memantine blocks alpha7* nicotinic acetylcholine receptors more potently than n-methyl-D-aspartate receptors in rat hippocampal neurons. J Pharmacol Exp Ther. 2005 Mar;312(3):1195-205. Epub 2004 Nov 2. [Article]
  2. Maskell PD, Speder P, Newberry NR, Bermudez I: Inhibition of human alpha 7 nicotinic acetylcholine receptors by open channel blockers of N-methyl-D-aspartate receptors. Br J Pharmacol. 2003 Dec;140(7):1313-9. doi: 10.1038/sj.bjp.0705559. [Article]
  3. Pohanka M: Alpha7 nicotinic acetylcholine receptor is a target in pharmacology and toxicology. Int J Mol Sci. 2012;13(2):2219-38. doi: 10.3390/ijms13022219. Epub 2012 Feb 17. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
Agonist
General Function
Potassium channel regulator activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.
Gene Name
DRD2
Uniprot ID
P14416
Uniprot Name
D(2) dopamine receptor
Molecular Weight
50618.91 Da
References
  1. Seeman P, Caruso C, Lasaga M: Memantine agonist action at dopamine D2High receptors. Synapse. 2008 Feb;62(2):149-53. [Article]
  2. Serra G, Demontis F, Serra F, De Chiara L, Spoto A, Girardi P, Vidotto G, Serra G: Memantine: New prospective in bipolar disorder treatment. World J Psychiatry. 2014 Dec 22;4(4):80-90. doi: 10.5498/wjp.v4.i4.80. [Article]
  3. Nakaya K, Nakagawasai O, Arai Y, Onogi H, Sato A, Niijima F, Tan-No K, Tadano T: Pharmacological characterizations of memantine-induced disruption of prepulse inhibition of the acoustic startle response in mice: involvement of dopamine D2 and 5-HT2A receptors. Behav Brain Res. 2011 Mar 17;218(1):165-73. doi: 10.1016/j.bbr.2010.11.053. Epub 2010 Dec 3. [Article]
  4. Mancini M, Ghiglieri V, Bagetta V, Pendolino V, Vannelli A, Cacace F, Mineo D, Calabresi P, Picconi B: Memantine alters striatal plasticity inducing a shift of synaptic responses toward long-term depression. Neuropharmacology. 2016 Feb;101:341-50. doi: 10.1016/j.neuropharm.2015.10.015. Epub 2015 Dec 3. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
Curator comments
This is a potential target. There are limited data regarding this target in the literature.
General Function
Voltage-gated cation channel activity
Specific Function
NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine. This protein plays a key role in synaptic p...
Gene Name
GRIN1
Uniprot ID
Q05586
Uniprot Name
Glutamate receptor ionotropic, NMDA 1
Molecular Weight
105371.945 Da
References
  1. Kotermanski SE, Wood JT, Johnson JW: Memantine binding to a superficial site on NMDA receptors contributes to partial trapping. J Physiol. 2009 Oct 1;587(Pt 19):4589-604. doi: 10.1113/jphysiol.2009.176297. Epub 2009 Aug 17. [Article]
Kind
Protein group
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
Curator comments
The binding of memantine to this target is believed to be low to negligible.
General Function
Inhibitory extracellular ligand-gated ion channel activity
Specific Function
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine...

Components:
References
  1. Molinaro G, Battaglia G, Riozzi B, Di Menna L, Rampello L, Bruno V, Nicoletti F: Memantine treatment reduces the expression of the K(+)/Cl(-) cotransporter KCC2 in the hippocampus and cerebral cortex, and attenuates behavioural responses mediated by GABA(A) receptor activation in mice. Brain Res. 2009 Apr 10;1265:75-9. doi: 10.1016/j.brainres.2009.02.016. Epub 2009 Feb 21. [Article]
  2. Memantine FDA label [File]
Kind
Protein group
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transmitter-gated ion channel activity
Specific Function
The glycine receptor is a neurotransmitter-gated ion channel. Binding of glycine to its receptor increases the chloride conductance and thus produces hyperpolarization (inhibition of neuronal firing).

Components:
References
  1. Xia P, Chen HS, Zhang D, Lipton SA: Memantine preferentially blocks extrasynaptic over synaptic NMDA receptor currents in hippocampal autapses. J Neurosci. 2010 Aug 18;30(33):11246-50. doi: 10.1523/JNEUROSCI.2488-10.2010. [Article]
  2. Limapichat W, Yu WY, Branigan E, Lester HA, Dougherty DA: Key binding interactions for memantine in the NMDA receptor. ACS Chem Neurosci. 2013 Feb 20;4(2):255-60. doi: 10.1021/cn300180a. Epub 2012 Dec 7. [Article]
  3. Memantine FDA label [File]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Data are based on the results of an in vitro study. Current information in the literature regarding this enzyme action is limited.
General Function
Steroid hydroxylase activity
Specific Function
Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Const...
Gene Name
CYP2A6
Uniprot ID
P11509
Uniprot Name
Cytochrome P450 2A6
Molecular Weight
56501.005 Da
References
  1. Micuda S, Mundlova L, Anzenbacherova E, Anzenbacher P, Chladek J, Fuksa L, Martinkova J: Inhibitory effects of memantine on human cytochrome P450 activities: prediction of in vivo drug interactions. Eur J Clin Pharmacol. 2004 Oct;60(8):583-9. doi: 10.1007/s00228-004-0825-1. Epub 2004 Sep 16. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
There is limited current data available on this enzyme inhibition, with the exception of one in vitro study.
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Micuda S, Mundlova L, Anzenbacherova E, Anzenbacher P, Chladek J, Fuksa L, Martinkova J: Inhibitory effects of memantine on human cytochrome P450 activities: prediction of in vivo drug interactions. Eur J Clin Pharmacol. 2004 Oct;60(8):583-9. doi: 10.1007/s00228-004-0825-1. Epub 2004 Sep 16. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Data are limited to the results of an in vitro study. Current information in the literature is limited.
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. Micuda S, Mundlova L, Anzenbacherova E, Anzenbacher P, Chladek J, Fuksa L, Martinkova J: Inhibitory effects of memantine on human cytochrome P450 activities: prediction of in vivo drug interactions. Eur J Clin Pharmacol. 2004 Oct;60(8):583-9. doi: 10.1007/s00228-004-0825-1. Epub 2004 Sep 16. [Article]
  2. Korhonen LE, Turpeinen M, Rahnasto M, Wittekindt C, Poso A, Pelkonen O, Raunio H, Juvonen RO: New potent and selective cytochrome P450 2B6 (CYP2B6) inhibitors based on three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis. Br J Pharmacol. 2007 Apr;150(7):932-42. doi: 10.1038/sj.bjp.0707173. Epub 2007 Feb 26. [Article]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Curator comments
This transporter is a potential transporter and has not been confirmed.
General Function
Quaternary ammonium group transmembrane transporter activity
Specific Function
Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creat...
Gene Name
SLC22A2
Uniprot ID
O15244
Uniprot Name
Solute carrier family 22 member 2
Molecular Weight
62579.99 Da
References
  1. Busch AE, Karbach U, Miska D, Gorboulev V, Akhoundova A, Volk C, Arndt P, Ulzheimer JC, Sonders MS, Baumann C, Waldegger S, Lang F, Koepsell H: Human neurons express the polyspecific cation transporter hOCT2, which translocates monoamine neurotransmitters, amantadine, and memantine. Mol Pharmacol. 1998 Aug;54(2):342-52. [Article]
  2. Muller F, Weitz D, Derdau V, Sandvoss M, Mertsch K, Konig J, Fromm MF: Contribution of MATE1 to Renal Secretion of the NMDA Receptor Antagonist Memantine. Mol Pharm. 2017 Sep 5;14(9):2991-2998. doi: 10.1021/acs.molpharmaceut.7b00179. Epub 2017 Aug 2. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Curator comments
This is a potential transporter and has not been confirmed.
General Function
Solute:proton antiporter activity
Specific Function
Involved in pH regulation to eliminate acids generated by active metabolism or to counter adverse environmental conditions. Major proton extruding system driven by the inward sodium ion chemical gr...
Gene Name
SLC9A1
Uniprot ID
P19634
Uniprot Name
Sodium/hydrogen exchanger 1
Molecular Weight
90762.13 Da
References
  1. Mehta DC, Short JL, Nicolazzo JA: Memantine transport across the mouse blood-brain barrier is mediated by a cationic influx H+ antiporter. Mol Pharm. 2013 Dec 2;10(12):4491-8. doi: 10.1021/mp400316e. Epub 2013 Oct 29. [Article]
  2. Mehta DC, Short JL, Nicolazzo JA: Reduced CNS exposure of memantine in a triple transgenic mouse model of Alzheimer's disease assessed using a novel LC-MS technique. J Pharm Biomed Anal. 2013 Nov;85:198-206. doi: 10.1016/j.jpba.2013.07.027. Epub 2013 Jul 30. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Curator comments
This is a potential transporter and has not been confirmed.
General Function
Symporter activity
Specific Function
Sodium-ion dependent, low affinity carnitine transporter. Probably transports one sodium ion with one molecule of carnitine. Also transports organic cations such as tetraethylammonium (TEA) without...
Gene Name
SLC22A4
Uniprot ID
Q9H015
Uniprot Name
Solute carrier family 22 member 4
Molecular Weight
62154.48 Da
References
  1. Mehta DC, Short JL, Nicolazzo JA: Memantine transport across the mouse blood-brain barrier is mediated by a cationic influx H+ antiporter. Mol Pharm. 2013 Dec 2;10(12):4491-8. doi: 10.1021/mp400316e. Epub 2013 Oct 29. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Curator comments
This is a potential transporter and has not been confirmed.
General Function
Monovalent cation:proton antiporter activity
Specific Function
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfat...
Gene Name
SLC47A1
Uniprot ID
Q96FL8
Uniprot Name
Multidrug and toxin extrusion protein 1
Molecular Weight
61921.585 Da
References
  1. Muller F, Weitz D, Derdau V, Sandvoss M, Mertsch K, Konig J, Fromm MF: Contribution of MATE1 to Renal Secretion of the NMDA Receptor Antagonist Memantine. Mol Pharm. 2017 Sep 5;14(9):2991-2998. doi: 10.1021/acs.molpharmaceut.7b00179. Epub 2017 Aug 2. [Article]

Drug created at June 13, 2005 13:24 / Updated at March 18, 2024 16:48